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Title: Angiopoietin-like 3 regulates hepatocyte proliferation and lipid metabolism in zebrafish

Highlights: • angptl3 is specifically expressed in the liver of developing zebrafish. • Knockdown of Angptl3 decreases liver size in developing zebrafish. • Knockdown of zebrafish Angptl3 elicits a hypocholesterolemia phenotype. - Abstract: Loss-of-function mutations in angiopoietin-like 3 (ANGPTL3) cause familial hypobetalipoproteinemia type 2 (FHBL2) in humans. ANGPTL3 belongs to the angiopoietin-like family, the vascular endothelial growth factor family that is structurally similar to angiopoietins and is known for a regulator of lipid and glucose metabolism, although it is unclear how mutations in ANGPTL3 lead to defect in liver development in the vertebrates. We report here that angptl3 is primarily expressed in the zebrafish developing liver and that morpholino (MO) knockdown of Angptl3 reduces the size of the developing liver, which is caused by suppression of cell proliferation, but not by enhancement of apoptosis. However, MO knockdown of Angptl3 did not alter angiogenesis in the developing liver. Additionally, disruption of zebrafish Angptl3 elicits the hypocholesterolemia phenotype that is characteristic of FHBL2 in humans. Together, our findings propose a novel role for Angptl3 in liver cell proliferation and maintenance during zebrafish embryogenesis. Finally, angptl3 morphants will serve as a good model for understanding the pathophysiology of FHBL2.
Authors:
 [1] ;  [2] ; ; ; ;  [3] ;  [4] ;  [2] ;  [3] ;  [1]
  1. Department of Biological Sciences, Sookmyung Women’s University, Seoul (Korea, Republic of)
  2. (Korea, Republic of)
  3. Department of Biology, Chungnam National University, Daejeon (Korea, Republic of)
  4. Department of Biomedical Sciences, Chonnam National University Medical School, Gwangju (Korea, Republic of)
Publication Date:
OSTI Identifier:
22416394
Resource Type:
Journal Article
Resource Relation:
Journal Name: Biochemical and Biophysical Research Communications; Journal Volume: 446; Journal Issue: 4; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANGIOGENESIS; APOPTOSIS; CELL PROLIFERATION; GLUCOSE; GROWTH FACTORS; HUMAN POPULATIONS; INHIBITION; LIPIDS; LIVER; LIVER CELLS; METABOLISM; MUTATIONS; PHENOTYPE; VERTEBRATES